Topical Dermatologic Pharmacology Foundations
Core concept: Topical therapy delivers drug directly to diseased skin, but the amount that reaches the target depends on the drug, its concentration, the vehicle, the thickness and integrity of the skin, occlusion, and the size of the treated area.
Key clinical distinction: Potency is a property of the finished product, not the molecule alone. The same corticosteroid can fall into a different potency class when it is formulated as an ointment rather than a lotion.
Prescribing priority: Match potency and vehicle to the lesion, body site, age, and duration of use, then prescribe a quantity and plan that the patient can follow and that limits cumulative exposure (Ernsthausen & Mills, 2026; Kennedy, 2026).
Why the Vehicle Matters
A topical vehicle affects penetration, tolerability, and adherence. Ointments are the most occlusive and hydrating, which increases penetration and makes them useful for dry, thick, or lichenified lesions. Creams are less occlusive and are often preferred for acute, moist-appearing lesions and for patients who will not tolerate a greasy product. Solutions, gels, foams, and shampoos spread easily over hair-bearing skin such as the scalp, foams and sprays are practical for genital areas, and lotions are the least occlusive (F.A. Davis Company, 2021b; Kennedy, 2026).
Occlusive products should generally be avoided on weeping lesions because they trap exudate (Ernsthausen & Mills, 2026). Changing vehicle can also change potency, so a switch from cream to ointment is a dose change as well as a cosmetic one. The best vehicle is often the one the patient will actually use. A cream during the day and an ointment at night is a reasonable compromise when greasiness is the barrier to adherence (Kennedy, 2026).
Skin Site and Absorption
Penetration is greatest where the stratum corneum is thin or the skin is occluded naturally, including the face, eyelids, axillae, groin, and other intertriginous areas. Penetration is poorest on the palms, soles, elbows, and knees. Lower-potency corticosteroids are therefore reserved for the face, skin folds, and genitals, while thick plaques on the extremities, palms, or soles often need higher potency to be effective (Ernsthausen & Mills, 2026; Kennedy, 2026).
Infants and young children have a higher ratio of body surface area to body weight and more permeable skin, which increases systemic exposure from topical products. Occlusion from diapers can act like an occlusive dressing. The same principles apply to older adults, whose thinner skin is more vulnerable to atrophy (Ernsthausen & Mills, 2026; Kennedy, 2026).
Topical Corticosteroids
Topical corticosteroids are nonspecific anti-inflammatory agents that reduce erythema, inflammation, and pruritus across a wide range of inflammatory skin conditions, including contact dermatitis, atopic dermatitis, and psoriasis. In the United States they are grouped into seven classes, from Class 1 (super-high potency) to Class 7 (least potent) (Ernsthausen & Mills, 2026).
| Class | Potency | Representative products |
| 1 | Super-high | Clobetasol propionate 0.05%; halobetasol propionate 0.05%; augmented betamethasone dipropionate 0.05% ointment |
| 2–3 | High to upper mid-strength | Fluocinonide 0.05%; desoximetasone 0.25%; mometasone furoate 0.1% ointment |
| 4–5 | Medium to lower mid-strength | Triamcinolone acetonide 0.1%; mometasone furoate 0.1% cream; fluticasone propionate 0.05% cream |
| 6–7 | Low to least potent | Desonide 0.05%; alclometasone 0.05%; hydrocortisone 0.5%–2.5% |
Adapted from Ernsthausen and Mills (2026). Potency classification varies by vehicle and concentration.
Selecting Potency
Potency is chosen according to the severity of disease, the thickness of the lesion, and the body site. High- or super-high-potency agents can be used briefly to gain control of thick or severe lesions on skin that tolerates them. Low-potency agents are appropriate for the face, intertriginous areas, infants, and young children. High- and super-high-potency products should generally be avoided in children (Ernsthausen & Mills, 2026; F.A. Davis Company, 2021a).
Once the condition improves, therapy should step down to the lowest potency and frequency that maintains control. Continuous use of super-high-potency agents is generally limited to a few weeks, and longer use of any potency calls for scheduled reassessment of benefit and local adverse effects (Elmets et al., 2021; Kennedy, 2026).
Tapering and Rebound
High-potency corticosteroids should not be stopped abruptly after prolonged use because rebound flares can occur. Tapering can be accomplished by moving to a lower-potency agent, reducing frequency, or both. In psoriasis, pulse or intermittent regimens, such as weekend-only application, can maintain improvement while limiting exposure (Elmets et al., 2021; F.A. Davis Company, 2021b).
Adverse Effects
Local adverse effects depend on potency, frequency, duration, site, and occlusion. Skin atrophy, striae, hypopigmentation, telangiectasia, and steroid-induced acne are the principal risks of long-term use. Application of potent agents over large areas, under occlusion, or on highly permeable skin increases the risk of systemic effects, including hypothalamic-pituitary-adrenal (HPA) axis suppression. This risk is especially relevant with high-potency agents used in wet-wrap therapy and in infants (Ernsthausen & Mills, 2026; F.A. Davis Company, 2021b). Patients should be told which product goes on which body site, how thinly to apply it, how long to use it, and what to do when the rash clears.
Topical Calcineurin Inhibitors
Tacrolimus ointment (0.03% and 0.1%) and pimecrolimus cream 1% inhibit calcineurin and block T-cell activation and release of proinflammatory cytokines. They do not cause the skin atrophy associated with corticosteroids, which makes them useful on the face, eyelids, and skin folds and in patients who need longer-term steroid-sparing therapy (Ernsthausen & Mills, 2026; Sidbury et al., 2023).
Tacrolimus ointment and pimecrolimus cream are approved for atopic dermatitis beginning at age 2, but tacrolimus strength is age dependent: 0.03% is used in children 2 to 15 years, while either 0.03% or 0.1% may be used from age 16 onward. They are also used off-label for facial and intertriginous psoriasis. Burning and stinging are common early and usually lessen with continued use. Both products carry a boxed warning regarding rare reports of malignancy, including skin cancer and lymphoma, although a causal relationship with topical use has not been established. Patients should limit ultraviolet exposure and avoid application to malignant or premalignant lesions (Ernsthausen & Mills, 2026; Kennedy, 2026).
Newer Nonsteroidal Topical Agents
Several nonsteroidal topical agents are now available, each with a specific mechanism and a narrower set of indications than topical corticosteroids. Crisaborole ointment (a phosphodiesterase-4 inhibitor) and ruxolitinib cream (a Janus kinase [JAK] inhibitor) are used for mild-to-moderate atopic dermatitis. Roflumilast cream (phosphodiesterase-4 inhibitor) and tapinarof cream (aryl hydrocarbon receptor agonist) are used for plaque psoriasis and, in newer formulations or indications, atopic dermatitis. Topical ruxolitinib shares the boxed warning of the JAK inhibitor class. These agents are discussed in the condition-specific pages (Davis et al., 2025; Ernsthausen & Mills, 2026; Kennedy, 2026).
Moisturizers and Emollients
Moisturizers are active therapy rather than cosmetic add-ons in atopic dermatitis, psoriasis, and dry-skin conditions. They restore barrier function and reduce transepidermal water loss. Ointments are the most occlusive, while lotions contain the most water and are the least effective for dry skin. Application after bathing, while the skin is still slightly damp, improves hydration (F.A. Davis Company, 2021b; Kapur et al., 2018).
Antipruritics, Astringents, and Keratolytics
Oral antihistamines have limited effect on the inflammatory pruritus of eczematous disease. First-generation agents such as diphenhydramine and hydroxyzine may be used briefly when nocturnal itching is severe, but their benefit is primarily sedative and must be weighed against anticholinergic effects, impaired attention, and next-day sedation. Topical antihistamines are generally avoided because they can sensitize the skin and cause contact dermatitis, and topical diphenhydramine should not be combined with oral diphenhydramine. Topical doxepin can reduce severe pruritus but may cause clinically important drowsiness (Ernsthausen & Mills, 2026; F.A. Davis Company, 2021b; Kapur et al., 2018).
Astringents such as aluminum acetate (Burow’s solution), calamine lotion, and witch hazel dry weeping lesions and relieve itching. Aluminum acetate is usually applied as a compress for about 30 minutes several times daily, and colloidal oatmeal baths are a safe soothing option (Ernsthausen & Mills, 2026).
Keratolytics such as salicylic acid soften scale and improve penetration of other topical agents. Salicylic acid can inactivate calcipotriene when they are combined, and salicylism is possible when it is applied over large areas or in patients with renal or hepatic impairment (Kennedy, 2026). Over-the-counter salicylic acid products for warts and corns range from about 5% to 17%, with 40% patches, and lactic acid 12% lotion applied twice daily treats xerosis, ichthyosis, and keratosis pilaris (F.A. Davis Company, 2021b).
Antiseborrheic Agents
Selenium sulfide and pyrithione zinc have cytostatic effects that slow epidermal cell turnover, ketoconazole is an antifungal, and sulfacetamide sodium is an antibacterial option for seborrheic skin. Medicated shampoos are applied to the scalp once or twice weekly and rinsed well, following product labeling (F.A. Davis Company, 2021b).
Other Topical and Related Agents
- Silver sulfadiazine: broad-spectrum topical anti-infective for burns; up to 10% may be absorbed from burned skin, and transient leukopenia can occur.
- Imiquimod and sinecatechins: topical immunomodulators for external anogenital warts; imiquimod is also used for actinic keratosis and superficial basal cell carcinoma.
- Podophyllum resin and silver nitrate: destructive agents applied in the office.
- Topical anesthetics: lidocaine-prilocaine, lidocaine-tetracaine, and lidocaine 4% for minor procedures.
- Topical minoxidil: for androgenetic alopecia; response takes at least 4 months, and new hair is lost within months of stopping.
- Oral finasteride: a type II 5-alpha-reductase inhibitor used with or instead of minoxidil for androgenetic alopecia in men; full effect takes 6 to 12 months, sexual adverse effects can occur, and treatment lowers prostate-specific antigen (PSA), which must be considered when PSA is interpreted. Finasteride is contraindicated in pregnancy, and pregnant patients should not handle crushed or broken tablets (F.A. Davis Company, 2021a).
- Aluminum chloride hexahydrate: for hyperhidrosis, applied at bedtime and washed off in the morning.
(F.A. Davis Company, 2021b)
High-Yield Distinctions
- Ointments are the most occlusive and penetrating vehicle; lotions and solutions suit hairy areas.
- A change in vehicle can change potency.
- Use the lowest effective potency on the face, skin folds, genitals, infants, and young children.
- Thick plaques, palms, and soles often need high-potency therapy.
- Taper high-potency corticosteroids after prolonged use to avoid rebound.
- Atrophy, striae, and HPA-axis suppression rise with potency, duration, area, and occlusion.
- Topical calcineurin inhibitors do not cause atrophy but carry a boxed warning.
- Moisturizers are part of treatment, not an optional extra.
- Topical antihistamines can cause sensitization and are not routinely recommended.
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References
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Kennedy, A. K. (2026). Psoriasis. In M. A. Chisholm-Burns, P. M. Malone, J. M. Kolesar, K. C. Lee, P. B. Bookstaver, & K. R. Matthias (Eds.), Pharmacotherapy principles & practice (7th ed., pp. 508–540). McGraw Hill.
Sidbury, R., Alikhan, A., Bercovitch, L., Cohen, D. E., Darr, J. M., Drucker, A. M., Eichenfield, L. F., Frazer-Green, L., Paller, A. S., Schwarzenberger, K., Silverberg, J. I., Singh, A. M., Wu, P. A., & Davis, D. M. R. (2023). Guidelines of care for the management of atopic dermatitis in adults with topical therapies. Journal of the American Academy of Dermatology, 89(1), e1–e20. https://doi.org/10.1016/j.jaad.2022.12.029